how long does immunity last?
posted on october 16, 2024 by dr kieran dee
dr kieran dee takes us behind the scenes of their latest publication 'smallpox vaccination campaigns resulted in age-associated population cross-immunity against monkeypox virus' published in journal of general virology.
how long does immunity last? once we have been infected by a pathogen and mounted an immune response against it, how long will the memory of that response persist? for some viruses this immune memory – and its effectiveness in protecting against infection - can be fleeting. but for poxviruses this memory can last for decades.
in july 2022, in response to unprecedented spread of monkeypox virus (mpxv), the world health organization (who) declared it a public health emergency of international concern. community spread of the virus was being recorded in the united kingdom. we thought it would be important to ascertain if there was any pre-existing immunity in the population that might confer protection against mpox disease. mpxv is an orthopoxvirus. other members of this family include the notorious variola virus (varv), the virus that causes smallpox, and the more innocuous vaccina virus (vacv), the virus on which the smallpox vaccine was based. these viruses are closely related, and an immune response raised against vacv will protect against smallpox. vaccination campaigns against smallpox were implemented in the uk until the 28th of july 1971, when it was officially announced that routine smallpox vaccination would end. based on previous reports of the longevity of smallpox vaccine induced immunity, we hypothesized that people who would have received the smallpox vaccine might have persisting immunity against other orthopoxviruses, including mpxv.
we studied serum samples from patients that had been collected between march 2020 and september 2022 during the covid-19 pandemic. sera was obtained from people at either primary (i.e. patients seen by a gp) or secondary care (i.e. patients admitted to hospital) in the national health service greater glasgow and clyde health board. these samples were originally collected to carry out serological surveillance on the prevalence of sars-cov-2 in the glasgow population.
all the serum samples we studied had key information associated to them. these included the year of birth of the patient, as well as the date on which samples were collected. our study included 430 samples taken from people born between 1919 and 2001. these samples were sub-divided by year of birth into groups, with 10 groups by 5-year intervals from 1919-1970, and 1 which was grouped by years of birth in or after 1971. the logic being, that the group born after 1971 shouldn’t have antibodies against either of these viruses. we first tested these samples for the presence, and their relative abundances, of antibodies that would bind vacv and mpxv proteins. we then compared the levels of these antibodies from each of the 10 groups born before 1971 against the group born after 1971. we observed that the age of the person correlated with the relative abundance of antibodies that bind both mpxv and vacv proteins (i.e. the older the person, the higher the antibody levels against mpxv and vacv). going one step further, we found a similar correlation between age and the capacity of the sera samples to neutralize infectious mpxv. so, the older that you are, the more likely you are to have immunity against mpxv. unsurprisingly, we also found that serum samples that had high neutralizing capacities against mpxv efficiently neutralized vacv too, with seemingly greater efficiency, which stands to reason as vacv is the basis of what people would have been vaccinated against originally.
while working on this, we uncovered something interesting. during a lab meeting in which we were presenting the data and beginning to see the trend of increased neutralization with age, one of the authors on the study, jordan bone, highlighted something to which we had previously been unaware. smallpox ceased to be endemic in the uk in the 1930s and mandatory vaccinations ended in 1948, but even up until then uptake was reported to be low in scotland. there was a small outbreak of smallpox in scotland in the spring of 1950. it was seeded by a sailor on a ship originating from india, where smallpox was still endemic. 19 people were infected and 6 died. this sparked a widespread vaccination campaign in the following weeks resulting in 300,000 people being vaccinated in the greater glasgow area, the same area from which our samples were sourced. in this context, it is interesting to note that the groups that had significantly higher levels of antibody and neutralization values compared to the group born after 1971 were all born before this mass vaccination event occurred. it is reasonable to speculate that this seemingly high number of positive serum samples is related to this mass vaccination event; and that if this is true then some elderly people of glasgow and lanarkshire may have some protection against mpox disease thanks to a vaccination that they received over half a century ago.
it is known that the presence of neutralizing antibodies against mpxv is a correlate of protection against severe mpox disease. it is also known that with immune senescence, the stregnth of the immune system is dampened as a person ages. so it is unclear if the anti-mpxv activity that we see in the lab would translate to robust protection against severe disease in vivo, especially in older people. while we can’t say with certainty if a person who received a vaccination against smallpox decades in the past would be protected from significant illness if they were to be exposed to mpxv today. what we do know is that when it comes to being infected with a poxvirus it is far more desirable to have pre-existing immunity.